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Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147810/1/art40762.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147810/2/art40762_am.pd

Intravenous Immunoglobulin for Hypogammaglobulinemia after Lung Transplantation: A Randomized Crossover Trial

Background We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG) after lung transplantation. Methods We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG), 10% Purified (Gamunex, Bayer, Elkhart, IN) monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG). The primary outcome was the number of bacterial infections within each treatment period. Results IVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24). There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001). Four serious adverse events (resulting in hospitalization) occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37). Chills, flushing, and nausea occurred during one infusion of IVIG. Conclusions Treatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown

Wave Function of a Brane-like Universe

Within the mini-superspace model, brane-like cosmology means performing the variation with respect to the embedding (Minkowski) time $\tau$ before fixing the cosmic (Einstein) time $t$. The departure from Einstein limit is parameterized by the 'energy' conjugate to $\tau$, and characterized by a classically disconnected Embryonic epoch. In contrast with canonical quantum gravity, the wave-function of the brane-like Universe is (i) $\tau$-dependent, and (ii) vanishes at the Big Bang. Hartle-Hawking and Linde proposals dictate discrete 'energy' levels, whereas Vilenkin proposal resembles $\alpha$-particle disintegration.Comment: Revtex, 4 twocolumn pages, 3 eps figures (accepted for publication in Class. Quan. Grav.

A Spitzer Study of Comets 2P/Encke, 67P/Churyumov-Gerasimenko, and C/2001 HT50 (LINEAR-NEAT)

We present infrared images and spectra of comets 2P/Encke, 67P/Churyumov-Gerasimenko, and C/2001 HT50 (LINEAR-NEAT) as part of a larger program to observe comets inside of 5 AU from the sun with the Spitzer Space Telescope. The nucleus of comet 2P/Encke was observed at two vastly different phase angles (20 degrees and 63 degrees). Model fits to the spectral energy distributions of the nucleus suggest comet Encke's infrared beaming parameter derived from the near-Earth asteroid thermal model may have a phase angle dependence. The observed emission from comet Encke's dust coma is best-modeled using predominately amorphous carbon grains with a grain size distribution that peaks near 0.4 microns, and the silicate contribution by mass to the sub-micron dust coma is constrained to 31%. Comet 67P/Churyumov-Gerasimenko was observed with distinct coma emission in excess of a model nucleus at a heliocentric distance of 5.0 AU. The coma detection suggests that sublimation processes are still active or grains from recent activity remain near the nucleus. Comet C/2001 HT50 (LINEAR-NEAT) showed evidence for crystalline silicates in the spectrum obtained at 3.2 AU and we derive a silicate-to-carbon dust ratio of 0.6. The ratio is an order of magnitude lower than that derived for comets 9P/Tempel 1 during the Deep Impact encounter and C/1995 O1 (Hale-Bopp).Comment: Accepted for publication in the Astrophysical Journal 48 pages, 15 figures, 10 table

Platelet activation in the postoperative period after lung transplantation

Objective During lung transplantation, cells in the pulmonary parenchyma are subjected to ischemia, hypothermic storage, and reperfusion injury. Platelets, whose granular contents include adhesion receptors, chemokines, and coactivating substances that activate inflammatory and coagulant cascades, likely play a critical role in the lung allograft response to ischemia and reperfusion. The platelet response to the pulmonary allograft, however, has never been studied. Here we report significant platelet activation immediately after lung transplantation. Methods We performed a prospective cohort study comparing markers of platelet activation in patients undergoing lung transplantation and patients undergoing nontransplant thoracotomy. Plasma levels of soluble P-selectin, soluble CD40 ligand, and platelet–leukocyte conjugates were measured before surgery, after skin closure, and at 6 postoperative hours. Results Both soluble P-selectin and soluble CD40 ligand levels increased significantly after lung transplantation but not after thoracotomy. Additionally, platelet–monocyte conjugate fluorescence was significantly higher after lung transplantation than after thoracotomy alone. Conclusion These findings suggest that platelet activation is significantly increased after lung transplantation beyond that expected from the postoperative state. The increase in circulating platelet–monocyte conjugates suggests an important interaction between platelets and inflammatory cells. Further research should examine whether platelet activation affects early graft function after lung transplantation

Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis

A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10–42) and 15(IQR 5–31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007–0.05%) in RA patients and by 0.008% (95% CI, 0.003–0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population

Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: design of a double-blind, randomised, placebo-controlled phase II trial

Introduction: Despite extensive multidisciplinary team (MDT) assessment, some patients have interstitial lung disease (ILD) that is considered unclassifiable (uILD), for which there are currently no approved treatments. This study will assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD. Methods and analysis: This double-blind, randomised, placebo-controlled phase II trial is enrolling adults with fibrosing ILD, including uILD that fulfils proposed research criteria for interstitial pneumonia with autoimmune features (IPAF), that cannot be classified with moderate or high confidence to any category of ILD following MDT discussion. Study participants must have >10% fibrosis on high-resolution CT scan within the previous 12 months, forced vital capacity (FVC) ≥45% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone vs placebo will be assessed by daily measurement of FVC using a handheld spirometer over the treatment period. Other functional parameters, patient-reported outcomes, samples for biomarker analysis and safety endpoints will be collected. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without IPAF. Ethics and dissemination: This trial is being conducted in accordance with the International Conference on Harmonisation E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws for countries in which the research is conducted